This application addresses broad Challenge Area (05) Comparative Effectiveness Research and specific Challenge Topic, 05-EB-101: Comparative Effectiveness of Advanced Imaging Procedures. The use of multimodality PET/CT or SPECT/CT has increased substantially in recent years. The use of both an anatomical imaging modality and a functional one provides an extra image dataset for diagnosis, can improve the reconstruction of the functional data, and can help localize tracer uptake by registering the two images. There is little doubt in the medical imaging community that multimodality imaging is beneficial. However, this benefit has not been objectively demonstrated and quantitatively measured for many applications or potential applications. There are also increased risks associated with using a second modality, for example, the increased radiation dose when a CT scan is added to a PET imaging study. Clinical studies that would demonstrate that the advantages of multimodality imaging outweigh the risks and costs are expensive, time consuming, and may require large numbers of patients. Retrospective studies in this area are limited by the rapid advancements in the technology used for CT and nuclear-medicine imaging, which implies that data for such studies is in short supply. The goal of the proposed work is to develop and test new methods for objectively evaluating the benefits and risks associated with multimodality imaging systems so that patients and physicians can make informed decisions about their use. These new methods will provide an inexpensive way to evaluate and compare multimodality imaging systems using task-based measures. The techniques and software that we develop can then be used to generate information that clinical researcher can use to focus their efforts in clinical studies. The tools developed under this proposal will be made freely available so that other researchers can use them in the design and evaluation of multimodality imaging systems and protocols for a variety of tasks and applications. PUBLIC HEALTH RELEVANCE: We will develop and validate methods that researchers can use to assess the benefits and risks associated with multimodality PET/CT and SPECT/CT imaging. The immediate impact of this work will be the availability of software for computing and comparing task performance using realistic models of imaging systems, relevant clinical tasks, and accurate patient models. This software will be made freely available so that other researchers can use it in the design and evaluation of multimodality imaging systems and protocols for a variety of tasks and applications.